Post-Approval Studies

Post-Approval Studies

In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).

The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.

CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.

In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.

The study is a prospective, multi-center, single arm clinical study that will be conducted in the United States and Europe.
The study is a prospective, multi-center, single arm clinical study that will be conducted in

the United States and Europe.

Study Population Description

Subjects ages > 18 or Age of Majority according to Law in states or countries where 18 is considered a minor and < 75 years seeking intervention for GERD who meet the study inclusion / exclusion criteria are eligible for this study. The study will consist of all IDE patients (100 subjects at the beginning of the IDE) available at the end of the IDE study (90 by time of the panel) that may be implanted with the device. Subjects entering study will be at least partially responsive to medical therapy (proton pump inhibitors) for their GERD symptoms and have tested positive (abnormal) in esophageal pH testing.

Subjects ages > 18 or Age of Majority according to Law in states or countries

where 18 is considered a minor and < 75 years seeking intervention for GERD who meet the study inclusion / exclusion criteria are eligible for this study. The study will consist of all IDE patients (100 subjects at the beginning of the IDE) available at the end of the IDE study (90 by time of the panel) that may be implanted with the device. Subjects entering study will be at least partially responsive to medical therapy (proton pump inhibitors) for their GERD symptoms and have tested positive (abnormal) in esophageal pH testing.

Sample Size

The study will continue to follow the 100 patients available in the IDE pivotal study. There were 90 patients available at time of panel discussion.
The study will continue to follow the 100 patients available in the IDE pivotal study.

There were 90 patients available at time of panel discussion.

Data Collection

Primary safety endpoint:

The primary safety endpoint is the rate of occurrence for serious device and procedure related adverse events. The primary safety end-point will be assessed by reporting all adverse events and by estimating the rate of serious device and procedure related adverse events through 12 months post implantation. Safety will also be evaluated by endoscopy to assess the mucosa and abdominal/chest X-ray evaluations to verify device location at 12 months post implantation.

Primary effectiveness endpoints:

Reduction in total distal esophageal acid exposure time defined by esophageal pH testing. Testing will be performed with subjects off PPIs. The subject¡¯s baseline pH acid exposure time will serve as the control and be compared to the subject¡¯s pH acid exposure time 12 months post implantation.

Success criteria ¨C At least 60% of subjects will have normalized or improved by at least 50% in total distal acid exposure.

Secondary effectiveness endpoints:

Subjects GERD-HRQL (Health Related Quality of Life) scores will be assessed off all GERD medications. The subject¡¯s baseline GERD-HRQL score will serve as the control and be compared to the subject¡¯s GERD-HRQL 12 months post implantation.

Success criteria - At least of subjects will have a reduction in total GERD-HRQL scores.

Subject¡¯s average daily dose of PPI will be evaluated. The subject¡¯s baseline average daily dosage will serve as the control and be compared to the subject¡¯s average daily dosage 12 months post-procedure.

Success criteria - At least of subjects will reduce their average daily PPI dosage .

Primary safety endpoint:

The primary safety endpoint is the rate of occurrence for serious device and

procedure related adverse events. The primary safety end-point will be assessed by reporting all adverse events and by estimating the rate of serious device and procedure related adverse events through 12 months post implantation. Safety will also be evaluated by endoscopy to assess the mucosa and abdominal/chest X-ray evaluations to verify device location at 12 months post implantation.

Primary effectiveness endpoints:

Reduction in total distal esophageal acid exposure time defined by esophageal pH testing. Testing will be performed with subjects off PPIs. The subject¡¯s baseline pH acid exposure time will serve as the control and be compared to the subject¡¯s pH acid exposure time 12 months post implantation.

Success criteria ¨C At least 60% of subjects will have normalized or improved by at least 50% in total distal acid exposure.

Secondary effectiveness endpoints:

Subjects GERD-HRQL (Health Related Quality of Life) scores will be assessed off all GERD medications. The subject¡¯s baseline GERD-HRQL score will serve as the control and be compared to the subject¡¯s GERD-HRQL 12 months post implantation.

Success criteria - At least of subjects will have a reduction in total GERD-HRQL scores.

Subject¡¯s average daily dose of PPI will be evaluated. The subject¡¯s baseline average daily dosage will serve as the control and be compared to the subject¡¯s average daily dosage 12 months post-procedure.

Success criteria - At least of subjects will reduce their average daily PPI dosage .

Followup Visits and Length of Followup

The length of follow up will be 60 months post-implantation.

The follow up assessments will take place at yearly intervals up to the end of the study at 60 months.

The length of follow up will be 60 months post-implantation.

The follow up assessments will

take place at yearly intervals up to the end of the study at 60 months.

Final Study Results

Actual Number of Patients Enrolled

100

Actual Number of Sites Enrolled

14

Patient Followup Rate

85/100 (85%)

Final Safety Findings

10 serious adverse events were reported in 7 subjects. The serious SAE rate was 7.0% with an upper confidence limit of 15.2% at 60 months.
10 serious adverse events were reported in 7 subjects. The serious SAE rate was 7.0%

with an upper confidence limit of 15.2% at 60 months.

Final Effectiveness Findings

83.3% of subjects had at least a 50% reduction in their 60 month total GERD-HRQL score when compared to baseline (95% confidence interval with lower confidence limit = 68.7%).
83.3% of subjects had at least a 50% reduction in their 60 month total GERD-HRQL

Strengths: This study had a high five year follow-up rate of 85 out of 100 subjects or 85%, which met the requirement of 80% specified in the condition of approval. It is important for a longitudinal study to

have a high follow-up rate, in order to avoid potential bias and generate valid conclusions.

Weaknesses: There was no comparator group in this study. The mean subject body mass index was 27.9 kg/m2 (range 19.8, 34.7). Therefore, the effectiveness of this device for patients with BMI over 35 is unknown.

Strengths: This study had a high five year follow-up rate of 85 out of 100

subjects or 85%, which met the requirement of 80% specified in the condition of approval. It is important for a longitudinal study to

have a high follow-up rate, in order to avoid potential bias and generate valid conclusions.

Weaknesses: There was no comparator group in this study. The mean subject body mass index was 27.9 kg/m2 (range 19.8, 34.7). Therefore, the effectiveness of this device for patients with BMI over 35 is unknown.

Recommendations for Labeling Changes

None. There are no new safety or effectiveness concerns since the approval of the current labeling